Magnetic resonance imaging (“MRI”) is a non-invasive method used to render images of the inside of an object. In medical applications, it is often used to demonstrate pathological or other physiological conditions or alterations of living tissues. As some examples only, in MRI techniques, contrast agents (“CA” or “CAs”) are used to estimate vascular properties such as blood flow, blood volume, and transfer constant of tissue microvessels, the latter being an index of the vascular permeability. However, the relationship between the contrast in the MRI image and the CA concentration is often not linear. Instead, it can depend on the nature of the sequence, the nature of the tissue, and the tissue concentration of contrast agent, limiting the reliability of estimates of vascular properties using MRI CAs.
Thus, although CAs are widely used in MRI studies, their ability to quantify such physiological variables as blood flow (Ostergaard et al. 1996a; Ostergaard et al. 1996b; Rempp et al. 1994), vascular volume (Boxerman et al. 2006; Rempp et al. 1994), and vascular transfer constant (Ewing et al. 2006; Tofts et al. 1999) can be limited by the mixed (e.g., T2* and T1), and/or nonlinear (Landis et al. 2000; Li X. et al. 2005; Yankeelov et al. 2003), contrast mechanisms encountered.
Currently, physiological measurements in humans most often employ chelated gadolinium in the form of Gd-DTPA or similar low-molecular weight CA. In animals, Gd-DTPA-albumin complex (Nagaraja et al. 2006) can be used in concentration-time studies to quantify tumor vascular transfer constant (K1 or Ktrans) and extravascular, extracellular leakage volume (ve). In humans, the concentration of CA is most commonly inferred from changes in T2* (Johnson et al. 2004; Ostergaard et al. 1996a; Ostergaard et al. 1996b; Rempp et al. 1994), although for purposes of measuring K1, the chosen mechanism may be that of T1 contrast (Daldrup-Link et al. 2004). However, as noted, changes in R2 (R2=1/T2) and R2* (R2*=1/T2*) and R1 (Landis et al. 2000; Li, X. et al. 2005; Yankeelov et al. 2003) (R1=1/T1) are not generally linear in CA concentration, particularly when CA occupies both vascular and extravascular tissue compartments. Since in MRI physiological studies, the measurement of CA concentration plays a crucial role in quantification and estimation of kinetic model parameters, these nonlinearities, if ignored, may lead to systematic errors that substantially undermine the reliability of the measurement.
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